Learn · Organic Chemistry

Deciding by the nucleophile/base

After the substrate, the reagent decides substitution vs elimination — and first- vs second-order.

Quick answer A strong unhindered nucleophile that is a weak base (CN⁻, N₃⁻, I⁻) drives SN2, while a strong bulky base (tert-butoxide, LDA, DBU) drives E2 toward the less-substituted Hofmann alkene. A weak neutral reagent that is often just the solvent (H₂O, ROH) can only manage SN1/E1, and only when the substrate ionizes on its own.

1. The reagent, not the substrate, sets substitution versus elimination.

Once you know the carbon, the species that attacks decides the fate of the reaction.

Cyanide — strong Nu, weak base → SN2
tert-Butoxide — strong bulky base → E2
Water — weak, neutral → SN1/E1

2. A strong, unhindered nucleophile that is a weak base gives SN2.

Cyanide, azide, thiolates, and iodide reach carbon faster than they grab a proton, so they substitute.

Cyanide — SN2
Azide — SN2
Iodide — SN2

3. A strong, bulky base gives E2 and the less-substituted Hofmann alkene.

tert-Butoxide, LDA, and DBU are too hindered to reach carbon, so they pluck a proton instead.

tert-Butoxide — bulky → E2 (Hofmann)

4. A strong base that is also a good nucleophile leans E2 on 2°/3° substrates.

Hydroxide and ethoxide can substitute, but crowded carbons push them to eliminate.

Hydroxide — mostly E2 on 2°/3°
Ethoxide — mostly E2 on 2°/3°

5. A weak, neutral reagent can only do SN1/E1, and only if the substrate ionizes.

Water and alcohols are often just the solvent, so they wait for a carbocation to form.

Water — SN1/E1
Ethanol — SN1/E1

6. Summary.

Strong Nu / weak base → SN2 · Strong bulky base → E2 (Hofmann) · Strong Nu-base on 2°/3° → E2 · Weak neutral reagent → SN1/E1.

Quiz yourself

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SN2. Azide is a strong, unhindered nucleophile but a weak base, so it substitutes.

E2 to the less-substituted (Hofmann) alkene, because the bulky base can't reach carbon and prefers the more accessible proton.

Water is a weak, neutral nucleophile/base, so it can't force a bimolecular step; it must wait for the substrate to ionize to a carbocation.

Mostly E2. Hydroxide is a strong base and decent nucleophile, but the crowded 3° carbon blocks backside attack, so elimination wins.

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